One-year outcome of bevacizumab therapy for chronic macular edema in central and branch retinal vein occlusions in real-world clinical practice in the UK

Background: The purpose of this study was to investigate the 12-month outcome of macular edema secondary to both chronic and new central and branch retinal vein occlusions treated with intravitreal bevacizumab in the real-life clinical setting in the UK. Methods: Retrospective case notes analysis of consecutive patients with retinal vein occlusions treated with bevacizumab in 2010 to 2012. Outcome measures were visual acuity (measured with Snellen, converted into logMAR [logarithm of the minimum angle of resolution] for statistical calculation) and central retinal thickness at baseline, 4 weeks post-loading phase, and at 1 year. Results: There were 56 and 100 patients with central and branch retinal vein occlusions, respectively, of whom 62% had chronic edema and received prior therapies and another 32% required additional laser treatments post-baseline bevacizumab. Baseline median visual acuity was 0.78 (interquartile range [IQR] 0.48–1.22) in the central group and 0.6 (IQR 0.3–0.78) in the branch group. In both groups, visual improvement was statistically significant from baseline compared to post-loading (P,0.001 and P=0.03, respectively), but was not significant by month 12 (P=0.058 and P=0.166, respectively); 30% improved by at least three lines and 44% improved by at least one line by month 12. Baseline median central retinal thickness was 449 μm (IQR 388–553) in the central group and 441 µm (IQR 357–501) in the branch group. However, the mean reduction in thickness was statistically significant at post-loading (P,0.001) and at the 12-month time point (P,0.001) for both groups. The average number of injections in 1 year was 4.2 in the central group and 3.3 in the branch group. Conclusion: Our large real-world cohort results indicate that bevacizumab introduced to patients with either new or chronic edema due to retinal vein occlusion can result in resolution of edema and stabilization of vision in the first year.

Comparison of Common Field/Clinical Measures to Standard Laboratory Measures of Hydration Status

Context: Accurately determining hydration status is a preventative measure for exertional heat illnesses (EHI). Objective: To determine the validity of various field measures of urine specific gravity (Usg) compared to laboratory instruments. Design: Observational research design to compare measures of hydration status: urine reagent strips (URS) and a urine color (Ucol) chart to a refractometer. Setting: We utilized the athletic training room of a Division I-A collegiate American football team. Participants: Trial 1 involved urine samples of 69 veteran football players (age=20.1+1.2yr; body mass=229.7+44.4lb; height=72.2+2.1in). Trial 2 involved samples from 5 football players (age=20.4+0.5yr; body mass=261.4+39.2lb; height=72.3+2.3in). Interventions: We administered the Heat Illness Index Score (HIIS) Risk Assessment, to identify athletes at-risk for EHI (Trial 1). For individuals “at-risk” (Trial 2), we collected urine samples before and after 15 days of pre-season “two-a-day” practices in a hot, humid environment(mean on-field WBGT=28.84+2.36oC). Main Outcome Measures: Urine samples were immediately analyzed for Usg using a refractometer, Diascreen 7® (URS1), Multistix® (URS2), and Chemstrip10® (URS3). Ucol was measured using Ucol chart. We calculated descriptive statistics for all main measures; Pearson correlations to assess relationships between the refractometer, each URS, and Ucol, and transformed Ucol data to Z-scores for comparison to the refractometer. Results: In Trial 1, we found a moderate relationship (r=0.491, p<.01) between URS1 (1.020+0.006μg) and the refractometer (1.026+0.010μg). In Trial 2, we found marked relationships for Ucol (5.6+1.6shades, r=0.619, p<0.01), URS2 (1.019+0.008μg, r=0.712, p<0.01), and URS3 (1.022+0.007μg, r=0.689, p<0.01) compared to the refractometer (1.028+0.008μg). Conclusions: Our findings suggest that URS were inconsistent between manufacturers, suggesting practitioners use the clinical refractometer to accurately determine Usg and monitor hydration status.

Investigating the Outcomes of a Physical Activity Program offered to Older Adults in South Florida and Understanding the Correlates of Completion

Despite the well-known benefits of physical activity, in 2012, only 37.5% of older adults aged 60 years or older met recommended aerobic physical activity levels and 16.1% met muscle-strengthening guidelines. Effective exercise programs can help combat the problem of inactivity but 50% of those who start participating in an exercise program drop out within first few weeks, preventing them from gaining any health benefits. Since fall 2008, the Healthy Aging Regional Collaborative of South Florida has offered EnhanceFitness (EF), an evidence-based physical activity program to older adults. This dissertation compared EF effectiveness at 4-, 8-, and 12-months and examined the factors that were associated with program completion. A paired sample t-test identified changes at 4-months and repeated measures design was used to identify changes from baseline to 4-, 8-, and 12- months. Logistic regression was used to identify correlates associated with completion. Between October 1, 2008 and December 31, 2012, 4,531 older adults (>=60 years) attended one or more EF sessions. Participants showed significant improvement in the number of chair stands performed in 30-seconds with mean change of 1.7, 1.6, and 2.0 respectively at 4-,8-,and 12- months (pp<0.001). Results suggest Black, non-Haitian men were less likely to complete the program when compared to white, non-Hispanic men (OR=0.41, p=0.02). Men who self-reported having at least one risk factor were more likely to complete the program (OR=1.81, p= 0.03). In addition, women who lived in Miami-Dade County (OR=2.13, ppppp<0.01). Effectiveness results revealed that all participants improved on outcome measures. However, improvement is more than double for those who completed recommended sessions (p

An evaluation of paediatric medicines reconciliation at hospital discharge into the community

OBJECTIVE: A UK national survey of primary care physicians has indicated that the medication information on hospital discharge summary was incomplete or inaccurate most of the time. Internationally, studies have shown that hospital pharmacist's interventions reduce these discrepancies in the adult population. There have been no published studies on the incidence and severity of the discrepancies of the medication prescribed for children specifically at discharge to date. The objectives of this study were to investigate the incidence, nature and potential clinical severity of medication discrepancies at the point of hospital discharge in a paediatric setting. METHODS: Five weeks prospective review of hospital discharge letters was carried out. Medication discrepancies between the initial doctor's discharge letter and finalised drug chart were identified, pharmacist changes were recorded and their severity was assessed. The setting of the review was at a London, UK paediatric hospital providing local secondary and specialist tertiary care. The outcome measures were: - incidence and the potential clinical severity of medication discrepancies identified by the hospital pharmacist at discharge. KEY FINDINGS: 142 patients (64 female and 78 males, age range 1 month - 18 years) were discharged on 501 medications. The majority of patients were under the care of general surgery and general paediatric teams. One in three discharge letters contained at least one medication discrepancy and required pharmacist interventions to rectify prior to completion. Of these, 1 in 10 had the potential for patient harm if undetected. CONCLUSIONS: Medicines reconciliation by pharmacist at discharge may be a good intervention in preventing medication discrepancies which have the potential to cause moderate harm in paediatric patients.

Usual medical treatments or levonorgestrel-IUS for women with heavy menstrual bleeding:long-term randomised pragmatic trial in primary care

Background: Heavy menstrual bleeding (HMB) is a common, chronic problem affecting women and health services. However, long-term evidence on treatment in primary care is lacking. Aim: To assess the effectiveness of commencing the levonorgestrel-releasing intrauterine system (LNG-IUS) or usual medical treatments for women presenting with HMB in general practice. Design and setting: A pragmatic, multicentre, parallel, open-label, long term, randomised controlled trial in 63 primary care practices across the English Midlands. Method: In total, 571 women aged 25–50 years, with HMB were randomised to LNG-IUS or usual medical treatment (tranexamic/mefenamic acid, combined oestrogen–progestogen, or progesterone alone). The primary outcome was the patient reported Menorrhagia Multi-Attribute Scale (MMAS, measuring effect of HMB on practical difficulties, social life, psychological and physical health, and work and family life; scores from 0 to 100). Secondary outcomes included surgical intervention (endometrial ablation/hysterectomy), general quality of life, sexual activity, and safety. Results: At 5 years post-randomisation, 424 (74%) women provided data. While the difference between LNG-IUS and usual treatment groups was not significant (3.9 points; 95% confidence interval = −0.6 to 8.3; P = 0.09), MMAS scores improved significantly in both groups from baseline (mean increase, 44.9 and 43.4 points, respectively; P<0.001 for both comparisons). Rates of surgical intervention were low in both groups (surgery-free survival was 80% and 77%; hazard ratio 0.90; 95% CI = 0.62 to 1.31; P = 0.6). There was no difference in generic quality of life, sexual activity scores, or serious adverse events. Conclusion: Large improvements in symptom relief across both groups show treatment for HMB can be successfully initiated with long-term benefit and with only modest need for surgery.

Non-Pharmacological Approaches for Pain Management in Sickle Cell Disease: Development of a Mindfulness-Based Intervention

Background: Sickle Cell Disease (SCD) is a genetic hematological disorder that affects more than 7 million people globally (NHLBI, 2009). It is estimated that 50% of adults with SCD experience pain on most days, with 1/3 experiencing chronic pain daily (Smith et al., 2008). Persons with SCD also experience higher levels of pain catastrophizing (feelings of helplessness, pain rumination and magnification) than other chronic pain conditions, which is associated with increases in pain intensity, pain behavior, analgesic consumption, frequency and duration of hospital visits, and with reduced daily activities (Sullivan, Bishop, & Pivik, 1995; Keefe et al., 2000; Gil et al., 1992 & 1993). Therefore effective interventions are needed that can successfully be used manage pain and pain-related outcomes (e.g., pain catastrophizing) in persons with SCD. A review of the literature demonstrated limited information regarding the feasibility and efficacy of non-pharmacological approaches for pain in persons with SCD, finding an average effect size of .33 on pain reduction across measurable non-pharmacological studies. Second, a prospective study on persons with SCD that received care for a vaso-occlusive crisis (VOC; N = 95) found: (1) high levels of patient reported depression (29%) and anxiety (34%), and (2) that unemployment was significantly associated with increased frequency of acute care encounters and hospital admissions per person. Research suggests that one promising category of non-pharmacological interventions for managing both physical and affective components of pain are Mindfulness-based Interventions (MBIs; Thompson et al., 2010; Cox et al., 2013). The primary goal of this dissertation was thus to develop and test the feasibility, acceptability, and efficacy of a telephonic MBI for pain catastrophizing in persons with SCD and chronic pain.

Methods: First, a telephonic MBI was developed through an informal process that involved iterative feedback from patients, clinical experts in SCD and pain management, social workers, psychologists, and mindfulness clinicians. Through this process, relevant topics and skills were selected to adapt in each MBI session. Second, a pilot randomized controlled trial was conducted to test the feasibility, acceptability, and efficacy of the telephonic MBI for pain catastrophizing in persons with SCD and chronic pain. Acceptability and feasibility were determined by assessment of recruitment, attrition, dropout, and refusal rates (including refusal reasons), along with semi-structured interviews with nine randomly selected patients at the end of study. Participants completed assessments at baseline, Week 1, 3, and 6 to assess efficacy of the intervention on decreasing pain catastrophizing and other pain-related outcomes.

Results: A telephonic MBI is feasible and acceptable for persons with SCD and chronic pain. Seventy-eight patients with SCD and chronic pain were approached, and 76% (N = 60) were enrolled and randomized. The MBI attendance rate, approximately 57% of participants completing at least four mindfulness sessions, was deemed acceptable, and participants that received the telephonic MBI described it as acceptable, easy to access, and consume in post-intervention interviews. The amount of missing data was undesirable (MBI condition, 40%; control condition, 25%), but fell within the range of expected missing outcome data for a RCT with multiple follow-up assessments. Efficacy of the MBI on pain catastrophizing could not be determined due to small sample size and degree of missing data, but trajectory analyses conducted for the MBI condition only trended in the right direction and pain catastrophizing approached statistically significance.

Conclusion: Overall results showed that at telephonic group-based MBI is acceptable and feasible for persons with SCD and chronic pain. Though the study was not able to determine treatment efficacy nor powered to detect a statistically significant difference between conditions, participants (1) described the intervention as acceptable, and (2) the observed effect sizes for the MBI condition demonstrated large effects of the MBI on pain catastrophizing, mental health, and physical health. Replication of this MBI study with a larger sample size, active control group, and additional assessments at the end of each week (e.g., Week 1 through Week 6) is needed to determine treatment efficacy. Many lessons were learned that will guide the development of future studies including which MBI strategies were most helpful, methods to encourage continued participation, and how to improve data capture.

Comparison between local anaesthetic agents, lidocaine and bupivacaine, in patients undergoing third molar extraction in terms of patient satisfaction.

AIMS: (1) To determine if anaesthetic agent bupivacaine, has a prolonged effect on the period of acute postoperative pain when compared to lidocaine, a shorter acting agent. (2) To determine patient’s post-operative satisfaction and preference with regard to anaesthetic choice. METHODS: This double blind, randomised, interventional clinical trial included 85 patients. All patients had bilateral impacted lower third molars of removed under general anaesthetic. All patients received 0.5% plain bupivacaine on one randomly allocated side, with 2% lidocaine (with adrenaline) administered on the opposite side. Pain was measured using visual analogue scales at 0, 30, 60 minutes and 3, 4, 6 and 8 hours post-surgery. Pain was analysed for 1 week following surgery. Psychological evaluations and patient reported outcomes, including patient satisfaction were evaluated. RESULTS: A significant difference in pain (P=0.001) was seen during the 3-8 hour post-operative period. The upper limit of the 95% confidence interval was 10.0 or above at 3hours and 4 hours post-surgery. Two-thirds of patients preferred bupivacaine. CONCLUSION: Longer lasting anaesthetics such as bupivacaine offer a longer period of analgesia, and improve overall patient satisfaction.

A study protocol of a randomised controlled trial to measure the effects of an augmented prescribed exercise programme (APEP) for frail older medical patients in the acute setting

Background: Older adults experience functional decline in hospital leading to increased healthcare burden and morbidity. The benefits of augmented exercise in hospital remain uncertain. The aim of this trial is to measure the short and longer-term effects of augmented exercise for older medical in-patients on their physical performance, quality of life and health care utilisation. Design and Methods: Two hundred and twenty older medical patients will be blindly randomly allocated to the intervention or sham groups. Both groups will receive usual care (including routine physiotherapy care) augmented by two daily exercise sessions. The sham group will receive stretching and relaxation exercises while the intervention group will receive tailored strengthening and balance exercises. Differences between groups will be measured at baseline, discharge, and three months. The primary outcome measure will be length of stay. The secondary outcome measures will be healthcare utilisation, activity (accelerometry), physical performance (Short Physical Performance Battery), falls history in hospital and quality of life (EQ-5D-5 L). Discussion: This simple intervention has the potential to transform the outcomes of the older patient in the acute setting.

Improved Accuracy in Optical Motion Capture Measurements Leads to Increased Sensitivity to Kinematic Changes

Clinical optical motion capture allows us to obtain kinematic and kinetic outcome measures that aid clinicians in diagnosing and treating different pathologies affecting healthy gait. The long term aim for gait centres is for subject-specific analyses that can predict, prevent, or reverse the effects of pathologies through gait retraining. To track the body, anatomical segment coordinate systems are commonly created by applying markers to the surface of the skin over specific, bony anatomy that is manually palpated. The location and placement of these markers is subjective and precision errors of up to 25mm have been reported [1]. Additionally, the selection of which anatomical landmarks to use in segment models can result in large angular differences; for example angular differences in the trunk can range up to 53o for the same motion depending on marker placement [2]. These errors can result in erroneous kinematic outcomes that either diminish or increase the apparent effects of a treatment or pathology compared to healthy data. Our goal was to improve the accuracy and precision of optical motion capture outcome measures. This thesis describes two separate studies. In the first study we aimed to establish an approach that would allow us to independently quantify the error among trunk models. Using this approach we determined if there was a best model to accurately track trunk motion. In the second study we designed a device to improve precision for test, re-test protocols that would also reduce the set-up time for motion capture experiments. Our method to compare a kinematically derived centre of mass velocity to one that was derived kinetically was successful in quantifying error among trunk models. Our findings indicate that models that use lateral shoulder markers as well as limit the translational degrees of freedom of the trunk through shared pelvic markers result in the least amount of error for the tasks we studied. We also successfully reduced intra- and inter-operator anatomical marker placement errors using a marker alignment device. The improved accuracy and precision resulting from the methods established in this thesis may lead to increased sensitivity to changes in kinematics, and ultimately result in more consistent treatment outcomes.

Longitudinal evaluation of quality of life in 288 patients with Neurofibromatosis 2

Advances in molecular biology have resulted in novel therapy for neurofibromatosis 2-related (NF2) tumours, highlighting the need for robust outcome measures. The disease-focused NF2 impact on quality of life (NFTI-QOL) patient questionnaire was assessed as an outcome measure for treatment in a multi-centre study. NFTI-QOL was related to clinician-rated severity (ClinSev) and genetic severity (GenSev) over repeated visits. Data were evaluated for 288 NF2 patients (n = 464 visits) attending the English national NF2 clinics from 2010 to 2012. The male-to-female ratio was equal and the mean age was 42.2 (SD 17.8) years. The analysis included NFTI-QOL eight-item score, ClinSev graded as mild, moderate, or severe, and GenSev as a rank order of the number of NF2 mutations (graded as mild, moderate, severe). The mean (SD) 8.7 (5.4) score for NFTI-QOL for either a first visit or all visits 9.2 (5.4) was similar to the published norm of 9.4 (5.5), with no significant relationships with age or gender. NFTI-QOL internal reliability was good, with a Cronbach’s alpha score of 0.85 and test re-test reliability r = 0.84. NFTI related to ClinSev (r = 0.41, p < 0.001; r = 0.46 for all visits), but weakly to GenSev (r = 0.16, p < 0.05; r = 0.15 for all visits). ClinSev related to GenSev (r = 0.41, p < 0.001; r = 0.42 for all visits). NFTI-QOL showed a good reliability and ability to detect significant longitudinal changes in the QOL of individuals. The moderate relationships of NFTI-QOL with clinician- and genetic-rated severity suggest that NFTI-QOL taps into NF2 patient experiences that are not encompassed by ClinSev rating or genotype.

Beyond maternal death: improving the quality of maternal care through national studies of ‘near-miss’ maternal morbidity

Knight M, Acosta C, Brocklehurst P, Cheshire A, Fitzpatrick K, Hinton L, Jokinen M, Kemp B, Kurinczuk JJ, Lewis G, Lindquist A, Locock L, Nair M, Patel N, Quigley M, Ridge D, Rivero-Arias O, Sellers S, Shah A on behalf of the UKNeS coapplicant group. Background Studies of maternal mortality have been shown to result in important improvements to women’s health. It is now recognised that in countries such as the UK, where maternal deaths are rare, the study of near-miss severe maternal morbidity provides additional information to aid disease prevention, treatment and service provision. Objectives To (1) estimate the incidence of specific near-miss morbidities; (2) assess the contribution of existing risk factors to incidence; (3) describe different interventions and their impact on outcomes and costs; (4) identify any groups in which outcomes differ; (5) investigate factors associated with maternal death; (6) compare an external confidential enquiry or a local review approach for investigating quality of care for affected women; and (7) assess the longer-term impacts. Methods Mixed quantitative and qualitative methods including primary national observational studies, database analyses, surveys and case studies overseen by a user advisory group. Setting Maternity units in all four countries of the UK. Participants Women with near-miss maternal morbidities, their partners and comparison women without severe morbidity. Main outcome measures The incidence, risk factors, management and outcomes of uterine rupture, placenta accreta, haemolysis, elevated liver enzymes and low platelets (HELLP) syndrome, severe sepsis, amniotic fluid embolism and pregnancy at advanced maternal age (≥ 48 years at completion of pregnancy); factors associated with progression from severe morbidity to death; associations between severe maternal morbidity and ethnicity and socioeconomic status; lessons for care identified by local and external review; economic evaluation of interventions for management of postpartum haemorrhage (PPH); women’s experiences of near-miss maternal morbidity; long-term outcomes; and models of maternity care commissioned through experience-led and standard approaches. Results Women and their partners reported long-term impacts of near-miss maternal morbidities on their physical and mental health. Older maternal age and caesarean delivery are associated with severe maternal morbidity in both current and future pregnancies. Antibiotic prescription for pregnant or postpartum women with suspected infection does not necessarily prevent progression to severe sepsis, which may be rapidly progressive. Delay in delivery, of up to 48 hours, may be safely undertaken in women with HELLP syndrome in whom there is no fetal compromise. Uterine compression sutures are a cost-effective second-line therapy for PPH. Medical comorbidities are associated with a fivefold increase in the odds of maternal death from direct pregnancy complications. External reviews identified more specific clinical messages for care than local reviews. Experience-led commissioning may be used as a way to commission maternity services. Limitations This programme used observational studies, some with limited sample size, and the possibility of uncontrolled confounding cannot be excluded. Conclusions Implementation of the findings of this research could prevent both future severe pregnancy complications as well as improving the outcome of pregnancy for women. One of the clearest findings relates to the population of women with other medical and mental health problems in pregnancy and their risk of severe morbidity. Further research into models of pre-pregnancy, pregnancy and postnatal care is clearly needed.

Patient perspectives of a diagnosis of myeloproliferative neoplasm in a case control study

Background: Myeloproliferative neoplasms (MPNs) including the classic entities; polycythemia vera (PV), essential thrombocythemia (ET) and primary myelofibrosis are rare diseases with unknown aetiology. The MOSAICC study, is an exploratory case–control study in which information was collected through telephone questionnaires and medical records. Methods: As part of the study, 106 patients with MPN were asked about their perceived diagnosis and replies correlated with their haematologist’s diagnosis. For the first time, a patient perspective on their MPN diagnosis and classification was obtained. Logistic regression analyses were utilised to evaluate the role of variables in whether or not a patient reported their diagnosis during interview with co-adjustment for these variables. Chi square tests were used to investigate the association between MPN subtype and patient reported categorisation of MPN. Results: Overall, 77.4 % of patients reported a diagnosis of MPN. Of those, 39.6 % recognised MPN as a ‘blood condition’,23.6 % recognised MPN as a ‘cancer’ and 13.2 % acknowledged MPN as an ‘other medical condition’. There was minimal overlap between the categories. Patients with PV were more likely than those with ET to report their disease as a ‘blood condition’. ET patients were significantly more likely than PV patients not to report their condition at all.Patients from a single centre were more likely to report their diagnosis as MPN while age, educational status, and WHO re-classification had no effect. Conclusions: The discrepancy between concepts of MPN in patients could result from differing patient interest in their condition, varying information conveyed by treating hematologists, concealment due to denial or financial concerns. Explanations for the differences in patient perception of the nature of their disease, requires further, larger scale investigation.

Withdrawal of Antidementia Drugs in Older People: Who, When and How?

The evidence base to guide withdrawal of antidementia medications in older people with dementia is limited; while some randomised controlled studies have considered discontinuation of cholinesterase inhibitors, no such studies examining discontinuation of the N-Methyl-D-aspartate receptor antagonist memantine have been conducted to date. The purpose of this opinion article was to summarise the existing evidence on withdrawal of cholinesterase inhibitors and memantine, to highlight the key considerations for clinicians when making these prescribing decisions and to offer guidance as to when and how treatment might be discontinued. Until the evidence-base is enhanced by the findings of large scale randomised controlled discontinuation trials of ChEIs and memantine which use multiple, clinically relevant cognitive, functional and behavioural outcome measures, clinicians’ prescribing decisions involve balancing the risks of discontinuation with side-effects and costs of continued treatment. Such decisions must be highly individualised and patient-centred.

Polymyalgia Rheumatica (PMR) Special Interest Group at OMERACT 11: outcomes of importance for patients with PMR

We worked toward developing a core outcome set for clinical research studies in polymyalgia rheumatica (PMR) by conducting (1) patient consultations using modified nominal group technique; (2) a systematic literature review of outcome measures in PMR; (3) a pilot observational study of patients presenting with untreated PMR, and further discussion with patient research partners; and (4) a qualitative focus group study of patients with PMR on the meaning of stiffness, using thematic analysis. (1) Consultations included 104 patients at 4 centers. Symptoms of PMR included pain, stiffness, fatigue, and sleep disturbance. Function, anxiety, and depression were also often mentioned. Participants expressed concerns about diagnostic delay, adverse effects of glucocorticoids, and fear of relapse. (2) In the systematic review, outcome measures previously used for PMR include pain visual analog scores (VAS), morning stiffness, blood markers, function, and quality of life; standardized effect sizes posttreatment were large. (3) Findings from the observational study indicated that asking about symptom severity at 7 AM, or "on waking," appeared more relevant to disease activity than asking about symptom severity "now" (which depended on the time of assessment). (4) Preliminary results were presented from the focus group qualitative study, encompassing broad themes of stiffness, pain, and the effect of PMR on patients' lives. It was concluded that further validation work is required before a core outcome set in PMR can be recommended. Nevertheless, the large standardized effect sizes suggest that pain VAS is likely to be satisfactory as a primary outcome measure for assessing response to initial therapy of PMR. Dissection of between-patient heterogeneity in the subsequent treatment course may require attention to comorbidity as a potential confounding factor.

Functional Magnetic Resonance Imaging Neurofeedback and Motor training for Parkinson’s Disease: Randomised Trial

Objective: Real-time functional magnetic resonance imaging (rt-fMRI) neurofeedback (NF) uses feedback of the patient’s own brain activity to self-regulate brain networks which in turn could lead to a change in behaviour and clinical symptoms. The objective was to determine the effect of neurofeedback and motor training and motor training (MOT) alone on motor and non-motor functions in Parkinson’s disease (PD) in a 10-week small Phase I randomised controlled trial. Methods: 30 patients with PD (Hoehn & Yahr I-III) and no significant comorbidity took part in the trial with random allocation to two groups. Group 1 (NF: 15 patients) received rt-fMRI-NF with motor training. Group 2 (MOT: 15 patients) received motor training alone. The primary outcome measure was the Movement Disorder Society – Unified Parkinson’s Disease Rating Scale-Motor scale (MDS-UPDRS-MS), administered pre- and post-intervention ‘off-medication’. The secondary outcome measures were the ‘on-medication’ MDS-UPDRS, the Parkinson’s disease Questionnaire-39, and quantitative motor assessments after 4 and 10 weeks. Results: Patients in the NF group were able to upregulate activity in the supplementary motor area by using motor imagery. They improved by an average of 4.5 points on the MDS-UPDRS-MS in the ‘off-medication’ state (95% confidence interval: -2.5 to -6.6), whereas the MOT group improved only by 1.9 points (95% confidence interval +3.2 to -6.8). However, the improvement did not differ significantly between the groups. No adverse events were reported in either group. Interpretation: This Phase I study suggests that NF combined with motor training is safe and improves motor symptoms immediately after treatment, but larger trials are needed to explore its superiority over active control conditions. Clinical Trial website : Unique Identifier: NCT01867827 URL: https://clinicaltrials.gov/ct2/show/NCT01867827?term=NCT01867827&rank=1